Vemurafenib has shown significant activity in V600 mutant melanoma; however the role of this agent in Lung adenocarcinoma with an activating BRAF mutation is still evolving.
Fusions of the anaplastic lymphoma receptor tyrosine kinase gene (ALK), ret proto-oncogene (RET), ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1), B-Raf proto-oncogene, serine/threonine kinase gene (BRAF), and neuregulin 1 gene (NRG1) and intronic MMNG HOS Transforming gene (MET) mutations are druggable oncogene alterations in lung adenocarcinoma that cause expression of aberrant transcripts.
The activating BRAF mutation p.V600E has been identified in many cancers, including colon and lung adenocarcinomas, papillary thyroid cancer, malignant melanoma, and hairy cell leukemia (HCL).
BRAF mutations occurred in 2.2% of advanced-stage lung adenocarcinomas, were most commonly V600E, and were associated with distinct clinicopathologic features in comparison with other genomic subtypes and with a high mutation rate in more than 1 gene.
In this series, 230 resected lung adenocarcinomas from smoker (>100 cigarettes in lifetime) at single center (Shanghai Cancer Center, Shanghai, China) were tested for mutation in EGFR, KRAS, BRAF, HER2, EML4-ALK and PIK3CA.
The aim of this study was to prospectively characterize the incidence of KRAS and BRAF mutations in EGFR FISH-positive surgically treated lung adenocarcinomas.
Combined genomic and proteomic analyses demonstrated infrequent alteration of validated lung cancer targets (including the absence of BRAF mutations in TTF1-negative LUAD), but identified novel potential targets for TTF1-negative LUAD, including KEAP1/Nrf2 and DNA repair pathways.
We examined the genome-wide expression profiles of 86 primary lung adenocarcinomas and compared them with the mutation status of the four key molecules (EGFR, ERBB2, KRAS and BRAF) in the EGFR/KRAS/BRAF pathway.
PLX8394 was effective against treatment-naive BRAF-mutant LAs and those with acquired vemurafenib resistance caused by an alternatively spliced, truncated BRAF<sup>V600E</sup> that promotes vemurafenib-insensitive MAPK pathway signaling.
<i>BRAF</i> V600E mutation, a missense mutation in exon 15 resulting in valine substitution for glutamate at position 600 within the kinase domain of BRAF oncogene, is found in a subset of lung adenocarcinoma (ADC).
In this surgical series, 52 resected lung adenocarcinomas from never-smokers (< 100 cigarettes in a lifetime) at a single institution (Fudan University, Shanghai, China) were analyzed concurrently for mutations in EGFR, KRAS, NRAS, HRAS, HER2, BRAF, ALK, PIK3CA, TP53 and LKB1.
Driver gene mutations in BRAF, EGFR, ERBB2, HRAS, KRAS, MET, NRAS, PIK3CA, STK11, and ephrin receptor genes (EPHA1-8, 10 and EPHB1-4, 6) were studied for both LAC and MM, and in BAP1, CUL1, CDKN2A, and NF2 for MM.